title: Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor.
abstract: OBJECTIVE
  In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d-amino acid oxidase inhibitor.
  
  
  OBJECTIVE
  To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.
  
  
  METHODS
  Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo.
  
  
  METHODS
  The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment.
  
  
  RESULTS
  Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects.
  
  
  CONCLUSIONS
  Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for d-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia.
authors.affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan2Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Lin
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hellemann
authors.forename: Chih-Chia
authors.initials: CC
authors.lastname: Huang
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Chen
authors.forename: Rene
authors.initials: R
authors.lastname: Tun
authors.forename: Yue-Cung
authors.initials: YC
authors.lastname: Chang
authors.forename: Guochuan E
authors.initials: GE
authors.lastname: Tsai
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005520:Food Preservatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*; D020160:Sodium Benzoate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D005520:Food Preservatives; D010919:Placebos; D016194:Receptors, N-Methyl-D-Aspartate; D003605:D-Amino-Acid Oxidase; D020160:Sodium Benzoate